Retinitis pigmentosa (RP) is a heterogeneous group of hereditary retinal degenerations (RDs) that affects 1 in 3,500 people worldwide. Age- related macular degeneration (AMD) affects as many as 1 in 4 people by the age of 75 and is the leading cause of blindness in people over age 50 in the US. There are currently no effective treatments to prevent photoreceptor degeneration and vision loss in patients with RP, or in most patients with AMD. Research efforts are being directed toward between understanding of the pathogenesis of these RDs and to develop therapies for them. The Sponsor's laboratory has recently demonstrated that subretinal injection of recombinant adeno-associated virus vectors for sustained injection of ribozymes in a rodent model of RP can delay photoreceptor loss and elevate a- and b-wave amplitudes in the ERG for at least 3 months. The relationship between rod and cone function with ribozymes, is largely unknown. The goals of the proposed experiments are to determine the duration of cone and rod photoreceptor survival and functional rescue by single and multiple administrations of ribozymes and to determine how late in the degenerative process ribozyme administration can rescue retinal function in S334ter and P23H rhodopsin mutant rat lines. These mutations in the rhodopsin gene are similar to those found in dominantly inherited human RP. We hypothesize that rescue of rod cell survival and function will also benefit cone cell survival and function. The proposed research and training plan provides enormous opportunities to help patients with both RP and AMD. The expertise the Candidate will gain using animal models of RD to develop and deliver therapies for RDs will be extremely valuable in her future career as an independent researcher.